Chapter 075. Evaluation and Management of Obesity (Part 6)

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Peripherally Acting Medications Orlistat (Xenical) is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin, produced by the mold Streptomyces toxytricini. Orlistat is a potent, slowly reversible inhibitor of pancreatic, gastric, and carboxylester lipases and phospholipase A2, which are required for the hydrolysis of dietary fat into fatty acids and monoacylglycerols. The drug acts in the lumen of the stomach and small intestine by forming a covalent bond with the active site of these lipases. Taken at a therapeutic dose of 120 mg tid, orlistat blocks the digestion and absorption of about 30% of dietary fat. After...

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Chapter 075. Evaluation and Management of Obesity (Part 6) Peripherally Acting Medications Orlistat (Xenical) is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin, produced by the mold Streptomyces toxytricini. Orlistat is a potent, slowly reversible inhibitor of pancreatic, gastric, and carboxylester lipases and phospholipase A2, which are required for the hydrolysis of dietary fat into fatty acids and monoacylglycerols. The drug acts in the lumen of the stomach and small intestine by forming a covalent bond with the active site of these lipases. Taken at a therapeutic dose of 120 mg tid, orlistat blocks the digestion and absorption of about 30% of dietary fat. After discontinuation of the drug, fecal fat usually returns to normal concentrations within 48–72 h.
Multiple randomized, 1–2 year double-blind, placebo-controlled studies have shown that after one year, orlistat produces a weight loss of about 9–10%, compared with a 4–6% weight loss in the placebo-treated groups. Because orlistat is minimally (
arachidonyl glyceride. Two cannabinoid receptors have been identified: CB 1 (abundant in the brain) and CB2 (present in immune cells). The brain endocannabinoid system is thought to control food intake through reinforcing motivation to find and consume foods with high incentive value and to regulate actions of other mediators of appetite. The first selective cannabinoid CB 1 receptor antagonist, rimonabant, was discovered in 1994. The medication antagonizes the orexigenic effect of THC and suppresses appetite when given alone in animal models. Several large prospective, randomized controlled trials have demonstrated the effectiveness of rimonabant as a weight-loss agent. Taken as a 20 mg dose, subjects lost an average of 6.5 kg (14.32 lb) compared to 1.5 kg (3.3 lb) for placebo at 1 year. Concomitant improvements were seen in waist circumference and cardiovascular risk factors. The most common reported side effects include depression, anxiety, and nausea. FDA approval of Rimonabant is still pending. Surgery Bariatric surgery can be considered for patients with severe obesity (BMI ≥40 kg/m2) or those with moderate obesity (BMI ≥35 kg/m2) associated with a serious medical condition. Surgical weight loss functions by reducing caloric intake and, depending on the procedure, macronutrient absorption. Weight-loss surgeries fall into one of two categories: restrictive and restrictive-malabsorptive (Fig. 75-2). Restrictive surgeries limit the amount of
food the stomach can hold and slow the rate of gastric emptying. The vertical banded gastroplasty (VBG) is the prototype of this category but is currently performed on a very limited basis due to lack of effectiveness in long-term trials. Laparoscopic adjustable silicone gastric banding (LASGB) has replaced the VBG as the most commonly performed restrictive operation. The first banding device, the lap-band, was approved for use in the United States in 2001. In contrast to previous devices, the diameter of this band is adjustable by way of its connection to a reservoir that is implanted under the skin. Injection or removal of saline into the reservoir tightens or loosens the band's internal diameter, thus changing the size of the gastric opening. Figure 75-2
Bariatric surgical procedures. Examples of operative interventions used for surgical manipulation of the gastrointestinal tract. A. Laparoscopic gastric band (LAGB). B. The Roux-en-Y gastric bypass. C. Biliopancreatic diversion with duodenal switch. D. Biliopancreatic diversion. (From ML Kendrick, GF Dakin. Surgical approaches to obesity. Mayo Clin Proc 815:518, 2006; with permission.)